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The metabolic syndrome

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This slideshow was presented in the 4th International Congress on CCM, January 2017, Tehran, IRAN

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The metabolic syndrome

  1. 1. THE METABOLIC SYNDROME Reza Nejat, M.D. Anesthesiologist, FCCM Former Assistant Prof., SBMU the 4th International Congress on CCM, January 2017, Tehran, IRAN
  2. 2. The Metabolic Syndrome  The Metabolic Syndrome:  the constellation of conditions which impose the patients to  AtheroSclerotic CardioVascular Diseases (ASCVD) for two-fold and  Type 2 Diabetes Mellitus (T2DM) in non-diabetics for five-fold the 4th International Congress on CCM, January 2017, Tehran, IRAN
  3. 3. The Metabolic Syndrome  Kylin, a Swedish physician as early as 1920s:  The combination of  hypertension,  hyperglycemia  hyperuricemia  was noticed as an entity with adverse outcome the 4th International Congress on CCM, January 2017, Tehran, IRAN
  4. 4. The Metabolic Syndrome  Professor Gerald M. Reaven, from Stanford University (1988):  the syndrome X  as the cluster of the conditions which could predispose the patients to both ASCVD and T2DM. the 4th International Congress on CCM, January 2017, Tehran, IRAN
  5. 5. The Metabolic Syndrome  Mets and high serum glucose level may play significant role in increasing the incidence ICU-acquired infections.  MetS increases ICU mortality the 4th International Congress on CCM, January 2017, Tehran, IRAN
  6. 6. The Metabolic Syndrome  defined by:  A cardiologist as  a “state of increased coronary heart disease risk’’;  A diabetologist as  a ‘‘prediabetic state”;  An endocrinologist as  an ‘‘insulin resistance state with dyslipidemia’’;  A hepatologist as  ‘‘nonalcoholic fatty liver disease’’;  A nephrologist as  ‘‘hypertension and prehypertension.’’ the 4th International Congress on CCM, January 2017, Tehran, IRAN
  7. 7. The Metabolic Syndrome  Names suggested:  cardiometabolic syndrome,  insulin resistance syndrome,  the deadly quartet  GHO Syndrome  Adult Treatment Panel III (ATP III) in 2001 and endorsed subsequently in 2014 by a group of experts :  “the metabolic syndrome” the 4th International Congress on CCM, January 2017, Tehran, IRAN
  8. 8. The Metabolic Syndrome  the diagnostic criteria:  not clustered according to prospective studies but with the aim of:  early identifying patients at risk  improving the outcome of the patient with changing of their lifestyle 1. Obesity 2. Hypertriglyceridemia 3. Hypertension 4. Glucose intolerance the 4th International Congress on CCM, January 2017, Tehran, IRAN
  9. 9. The Metabolic Syndrome  Definition of the Metabolic Syndrome proposed by IDF:  central obesity (Hyper-weight) plus any two of the following 4 criteria: a) Hyper-TG b) Hypo-HDL cholesterol c) Hyper-glycemia d) Hyper-tension the 4th International Congress on CCM, January 2017, Tehran, IRAN
  10. 10. The Metabolic Syndrome  Obesity quantitatively determined by: body mass index (BMI)  𝑩𝑩𝑩𝑩𝑩𝑩 = 𝑾𝑾𝑾𝑾𝑾𝑾 𝑾𝑾 𝑾𝑾𝑾𝑾 𝑲𝑲𝑲𝑲 𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯 𝒎𝒎 𝟐𝟐  25 ≤BMI≤ 29.9  overweight  30 ≤BMI≤ 34.9  obesity  35 ≤BMI≤ 40  morbid obesity  Ideal BMI < 25  the lower cuff point of ideal BMI is not defined yet. the 4th International Congress on CCM, January 2017, Tehran, IRAN
  11. 11. The Metabolic Syndrome  Central obesity or increasing the waist circumference:  waist circumference (European) i. ≥ 94 cm (male), ii. ≥80 cm (female)  waist circumference (Asian) i. ≥ 90 cm (male), ii. ≥80 cm (female)  waist circumference (USA) i. ≥ 102 cm (male) ii. ≥ 88 cm (female) the 4th International Congress on CCM, January 2017, Tehran, IRAN
  12. 12. The Metabolic Syndrome  Definition of the Metabolic Syndrome proposed by IDF:  central obesity (Hyper-weight) plus any two of the following 4 criteria: 1) Hyper-TG, 2) Hypo-HDL cholesterol, 3) Hyper-glycemia 4) Hyper-tension  Hyper-TG  TG ≥ 150 mg/dl (1·7 mmol/L) or  specific treatment for this lipid abnormality the 4th International Congress on CCM, January 2017, Tehran, IRAN
  13. 13. The Metabolic Syndrome  Definition of the Metabolic Syndrome proposed by IDF:  central obesity (Hyper-weight) plus any two of the following 4 criteria: 1) Hyper-triglyceridemia, 2) Hypo-HDL cholesterol, 3) Hyper-glycemia 4) Hyper-tension  Hypo-HDL cholesterol  < 40 mg/dl (1·03 mmol/L) (male)  < 50 mg/dl (1·29 mmol/L) (female) the 4th International Congress on CCM, January 2017, Tehran, IRAN
  14. 14. The Metabolic Syndrome  Definition of the Metabolic Syndrome proposed by IDF:  central obesity (Hyper-weight) plus any two of the following 4 criteria: 1) Hyper-triglyceridemia, 2) Hypo-HDL cholesterol, 3) Hyper-glycemia 4) Hyper-tension  Hyper-glycemia  FPG≥ 100 md/dl (5.6 mmol/L) or  previously diagnosed T2DM the 4th International Congress on CCM, January 2017, Tehran, IRAN
  15. 15. The Metabolic Syndrome  Definition of the Metabolic Syndrome proposed by IDF:  central obesity (Hyper-weight) plus any two of the following 4 criteria: 1) Hyper-triglyceridemia, 2) Hypo-HDL cholesterol, 3) Hyper-glycemia 4) Hyper-tension  Hyper-tension  Blood pressure ≥130/85 (mmHg) or  treatment of previously diagnosed hypertension the 4th International Congress on CCM, January 2017, Tehran, IRAN
  16. 16. The Metabolic Syndrome  The Metabolic Syndrome criteria in children and adolescents: 1. Obesity (visceral); 2. Hypertension; 3. Hyperinsulinemia/insulin resistance, IGT/type 2 diabetes mellitus; 4. Dyslipidemia (hyper-TG, low HDL cholesterol)  the cutoff values generally differ from study to study and abdominal obesity is not well defined  FAMILY Hx (>50% were over-weight with dyslipemia) the 4th International Congress on CCM, January 2017, Tehran, IRAN
  17. 17. The Metabolic Syndrome  Has been associated with:  essential hypertension,  lung dysfunction due to abdominal obesity,  chronic kidney disease,  polycystic ovary syndrome (PCOD),  nonalcoholic fatty liver disease (NAFLD),  certain forms of cancer,  obstructive sleep apnea,  cholesterol gallstones,  gout,  depression,  musculosketal disease the 4th International Congress on CCM, January 2017, Tehran, IRAN
  18. 18. The Metabolic Syndrome  Does the brain shrink as the waist expands?  Higher adiposity:  frontal GM atrophy across all ages  parietal and temporal GM atrophy in middle and old age. the 4th International Congress on CCM, January 2017, Tehran, IRAN
  19. 19. The Metabolic Syndrome  prevalence:  cannot be determined accurately:  No precise definition of the metabolic syndrome  The cutoff point relevant to each criteria differs in different populations  In adults: from 10% to 40%  In children: 2-9% in General Population to 12-44% in overweight children  most often seen in populations with:  excessive caloric intake  sedentary life style the 4th International Congress on CCM, January 2017, Tehran, IRAN
  20. 20. The Metabolic Syndrome  in IRANian population:  more prevalent in 60-69 year age-group than in 20-29 year age-group  Azizi F, et al. Diabetes Res Clin Pract (2003) 61: 29–37  consistent with the epidemiological findings in the USA and France  Eckel R. H., et al. Lancet (2005) 365: 1415–28  ranges from 10-60% depending on the age, gender, region  Hajian-Tilaki K. Caspian J Intern Med. 2015; 6(2): 51-61 the 4th International Congress on CCM, January 2017, Tehran, IRAN
  21. 21. The Metabolic Syndrome  Clinical Presentation:  Physical inactivity,  Obesity,  Ageing  Hormonal Imbalance  may present in variable ways:  which component of its criteria takes the dominant feature? atherogenic dyslipidemia, elevated blood pressure and dysglycemia:  ASCVD as the clinical presentation the 4th International Congress on CCM, January 2017, Tehran, IRAN
  22. 22. The Metabolic Syndrome  Obesity  is a true risk factor for the metabolic syndrome; NOT THE CAUSE;  Non-obese have metabolic risk factors, too!!!  took precedence among the other contributing factors  predisposes to insulin resistance  Non-obese might be resistant to insulin, too!!!  Over-eating or over-nutrition:  the mainstay of the syndrome the 4th International Congress on CCM, January 2017, Tehran, IRAN
  23. 23. The Metabolic Syndrome  Fat normally settles down in adipose tissue.  Excess of fat is distributed ectopically in the liver and muscles  Over-nutrition provides ectopic fat the 4th International Congress on CCM, January 2017, Tehran, IRAN
  24. 24. The Metabolic Syndrome  Obesity might occur:  in the upper part of the body  (apple-shaped body)  in the lower part of the body  (pear-shaped body)  APPLE-SHAPED obesity, predisposes to:  the metabolic syndrome  visceral fat more than subcutaneous fat the 4th International Congress on CCM, January 2017, Tehran, IRAN
  25. 25. The Metabolic Syndrome the 4th International Congress on CCM, January 2017, Tehran, IRAN  upper-body adipose tissue: supplies ectopic fat releasing non-esterified fatty acids (NEFA)  Liver o Metabolizes these FAs, o Re-erterifizes these Fas, o Incorporates NEFA in VLDL as TRIGLYSERIDES.
  26. 26. The Metabolic Syndrome  Insulin in Critically ill patients (CIP) has: potent anti-inflammatory effects protect against organ damage Hyperglycemia in CIP: glucagon, growth hormone, catecholamines, glucocorticoids and cytokines such as IL-1, IL-6 and TNF-α, dextrose and nutritional support Insulin deficiency Insulin resistance (TRIB3 gene product) Increased gluconeogenesis the 4th International Congress on CCM, January 2017, Tehran, IRAN
  27. 27. The Metabolic Syndrome Insulin resistance:  reduced sensitivity to the metabolic effects of insulin  leads to the impaired insulin-stimulated glucose uptake and oxidation, uncontrolled hepatic glucose production  increases T2DM, CVSD, NAFLD, NASH, malignancies Its severity may vary for sixfold??!! the 4th International Congress on CCM, January 2017, Tehran, IRAN
  28. 28. The Metabolic Syndrome the 4th International Congress on CCM, January 2017, Tehran, IRAN
  29. 29. The Metabolic Syndrome Insulin resistance: How to Dx?  Euglycemic hyperinsulinemic clamp (the best way)  Homeostatic model assessment-insulin resistance (HOMA-IR) index and 𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 − 𝐼𝐼 𝐼𝐼 = [𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼 𝑈𝑈 𝑚𝑚𝑚𝑚 × 𝐵𝐵𝐵𝐵 𝑚𝑚𝑚𝑚 𝑑𝑑𝑑𝑑 ]/405  Quantitative insulin sensitivity check index(QUICKI) 𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄 𝑄𝑄𝑄𝑄 = 1/[log 𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼 𝑈𝑈 𝑚𝑚𝑚𝑚 + log 𝐵𝐵𝐵𝐵( 𝑚𝑚𝑚𝑚 𝑑𝑑𝑑𝑑 )] the 4th International Congress on CCM, January 2017, Tehran, IRAN
  30. 30. The Metabolic Syndrome White Adipose Tissue:  extensive communicative system with other tissues and organs.  Adipocyte direct signal to other tissues: skeletal muscle the adrenal cortex.  a distinct cross-talk between white adipocytes and the brain through leptin and the sympathetic nervous system. the 4th International Congress on CCM, January 2017, Tehran, IRAN
  31. 31. The Metabolic Syndrome  White Adipose Tissue  is not just a fuel storage  is an endocrine organ  secrets several major hormones (SECRETOMES)  In a autocrine/paracrine fashion  proteins implicated in neuroendocrine and immunity  ADIPOCYTOKINES  ADIPOKINOMES  ADIPOKINES  Leptin  Adiponectin the 4th International Congress on CCM, January 2017, Tehran, IRAN
  32. 32. The Metabolic Syndrome  SECRETOMES:  adipokines together with lipid moieties released, such as fatty acids and prostaglandins,  ADIPOKINES (over fifty):  classical cytokines (TNFa, IL-6, IL-8),  growth factors [transforming growth factor-β (TGF-β), FGF21]  proteins of the alternative complement system (adipsin, acylation-stimulating protein) the 4th International Congress on CCM, January 2017, Tehran, IRAN
  33. 33. The Metabolic Syndrome  ADIPOKINES, involved in :  vascular hemostasis (plasminogen activator inhibitor-1 (PAI-1), tissue factor),  the regulation of blood pressure (angiotensinogen, mineralocorticoids)  lipid metabolism (retinol-binding protein, cholesteryl ester transfer protein),  glucose homeostasis (adiponectin, possibly resistin) and  angiogenesis (vascular endothelial growth factor; VEGF),  acute-phase and stress reactants (haptoglobin, metallothionein) the 4th International Congress on CCM, January 2017, Tehran, IRAN
  34. 34. The Metabolic Syndrome  Adiponectine:  synthesised only in adipose tissue  With anti-atherogenic and anti- inflammatory effects  With inhibitory implication on phagocytic activity and TNFα production  falls in obesity and T2DM  inversely related to insulin resistance the 4th International Congress on CCM, January 2017, Tehran, IRAN
  35. 35. The Metabolic Syndrome  TNF-α in obesity, involved in:  insulin resistance,  chronic low-grade inflammatory state  has inhibitory effect on the insulin receptor signaling pathway  stimulate CRP release from the liver;  CRP level rises with BMI and falls with weight loss  Secretion of nerve growth factor (NGF) associated with atherosclerosis and wound healing  Apoptosis  Production of IL-6 and Haptoglobulin the 4th International Congress on CCM, January 2017, Tehran, IRAN
  36. 36. The Metabolic Syndrome IL-6 is expressed in and secreted by adipocytes: has local actions within WAT released into the circulation  IL-6 expression in WAT: elevated in obesity and insulin resistance conveying information from adipocytes to the hypothalamus regulating balance of energy the 4th International Congress on CCM, January 2017, Tehran, IRAN
  37. 37. The Metabolic Syndrome  TGF-β, of pleiotropic growth factor family with:  immuno-regulatory properties  malignancies,  autoimmune disorders,  susceptibility to opportunistic infections and  fibrotic complications in chronic inflammatory conditions the 4th International Congress on CCM, January 2017, Tehran, IRAN
  38. 38. The Metabolic Syndrome  PAI-1:  synthesis in WAT is raised in obesity  SAA:  major acute-phase reactants  pro-inflammatory and anti- inflammatory  CRP:  WAT a major player in the raised circulating levels of CRP in obesity,  through the indirect route of adipocyte-derived IL-6 the 4th International Congress on CCM, January 2017, Tehran, IRAN
  39. 39. The Metabolic Syndrome  Leptin:  Secreted by adipose tissue  Crosses BBB readily  Signals to the brain of the status of body energy stores  Inhibit food intake  Leptin deficiency and resistance the 4th International Congress on CCM, January 2017, Tehran, IRAN
  40. 40. The Metabolic Syndrome the 4th International Congress on CCM, January 2017, Tehran, IRAN  rezanejat.com  icuaticu.com  2icuedu.com
  41. 41. EKG the 4th International Congress on CCM, January 2017, Tehran, IRAN

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